Thermostable vaccine compositions and methods of preparing same

Abstract

Compositions relating to thermostable vaccines and methods of preparing the same. Specifically, methods of preparing thermostable vaccines based on a recombinant ricin neurotoxin protein and uses of co-adjuvants to develop a composition capable of eliciting an immune response in a subject.

What is claimed is: 
     
       1. A frozen immunogenic composition, comprising:
 (a) at least one aluminum-salt adjuvant; 
 (b) at least one buffering agent wherein the buffering agent comprises a buffering salt, the at least one buffering agent selected from the group consisting of succinate, citrate, prolamine, arginine, glycine, histidine, and phosphate; 
 (c) at least one volatile salt, the volatile salt selected from the group consisting of ammonium acetate, ammonium formate, ammonium carbonate, ammonium bicarbonate, triethylammonium acetate, triethylammonium formate, triethylammonium carbonate, trimethylamine acetate trimethylamine formate, trimethylamine carbonate, pyridinal acetate and pyridinal formate; 
 (d) at least one glass forming agent, the glass forming agent selected from the group consisting of trehalose, sucrose, ficoll, dextran, maltotriose, lactose, mannitol and glycine, hydroxyethyl starch, and glycine; 
 (e) at least one immunologically-active co-adjuvant; and 
 (f) at least one antigen, wherein the immunogenic composition is frozen. 
 
     
     
       2. The frozen immunogenic composition of  claim 1 , wherein the at least one aluminum-salt adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate and aluminum sulfate. 
     
     
       3. The frozen immunogenic composition of  claim 1 , wherein anions of the at least one buffering agent is are selected from the group consisting of citrate, glycine, histidine, and phosphate. 
     
     
       4. The frozen immunogenic composition of  claim 1 , wherein the at least one glass-forming agent is selected from the group consisting of trehalose, sucrose, ficoll, dextran, mannitol and glycine, and hydroxyethyl starch. 
     
     
       5. The frozen immunogenic composition of  claim 1 , wherein the at least one immunologically-active co-adjuvant is selected from the group consisting of lipid A, lipid A derivatives, monophosphoryl lipid A, chemical analogues of monophosphoryl Lipid A, CpG containing oligonucleotides, TLR-4 agonists, flagellin, flagellins derived from gram negative bacteria, TLR-5 agonists, fragments of flagellins capable of binding to TLR-5 receptors, saponins, analogues of saponins, QS-21, purified saponin fractions, ISCOMS and saponin combinations with sterols and lipids. 
     
     
       6. The frozen immunogenic composition of  claim 1 , wherein the antigen is selected from, or derived from the group consisting of rotavirus, foot and mouth disease virus, influenza A virus, influenza B virus, influenza C virus, H1N1, H2N2, H3N2, H5N1, H7N7, HIN2, H9N2, H7N2, H7N3, H1ON7, human parainfluenza type 2, herpes simplex virus, Epstein-Barr virus, varicella virus, porcine herpesvirus 1, cytomegalovirus, lyssavirus,  Bacillus anthracis , anthrax PA and derivatives thereof, poliovirus, Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis E, distemper virus, Venezuelan equine encephalomyelitis, feline leukemia virus, reovirus, respiratory syncytial virus, Lassa fever virus, polyoma tumor virus, canine parvovirus, papilloma virus, tick borne encephalitis virus, rinderpest virus, human rhinovirus species, Enterovirus species, Mengo virus, paramyxovirus, avian infectious bronchitis virus, human T-cell leukemia-lymphoma virus 1, human immunodeficiency virus-1, human immunodeficiency virus-2, lymphocytic choriomeningitis virus, parvovirus B19, adenovirus, rubella virus, yellow fever virus, dengue virus, bovine respiratory syncytial virus, coronavirus,  Bordetella pertussis, Bordetella bronchiseptica, Bordetella parapertussis, Brucella abortis, Brucella melitensis, Brucella suis, Brucella ovis, Brucella species, Escherichia coli, Salmonella species, Salmonella typhi , Streptococci,  Vibrio cholera, Vibrio parahaemolyticus, Shigella, Pseudomonas, tuberculosis, avium, Bacille Calmette Guerin, Mycobacterium leprae , Pneumococci, Staphlylococci,  Enterobacter  species,  Rochalimaia henselae, Pasteurella haemolytica, Pasteurella multocida, Chlamydia trachomatis, Chlamydia psittaci, Lymphogranuloma venereum, Treponema pallidum, Haemophilus species, Mycoplasma bovigenitalium, Mycoplasma pulmonis, Mycoplasma species, Borrelia burgdorferi, Legionalla pneumophila, Colstridium botulinum, Corynebacterium diphtheriae, Yersinia entercolitica, Rickettsia rickettsii, Rickettsia typhi, Rickettsia prowsaekii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Schistosomes, trypanosomes, Leishmania species, Filarial nematodes, trichomoniasis, sarcosporidiasis, Taenia saginata, Taenia solium, Leishmania, Toxoplasma gondii, Trichinella spiralis, coccidiosis, Eimeria tenella, Cryptococcus neoformans, Candida albican, Apergillus fumigatus, coccidioidomycosis, Neisseria gonorrhoeae , malaria circumsporozoite protein, malaria merozoite protein, trypanosome surface antigen protein, pertussis, alphaviruses, adenovirus, diphtheria toxoid, tetanus toxoid, meningococcal outer membrane protein, streptococcal M protein, Influenza hemagglutinin, cancer antigen, tumor antigens, toxins,  Clostridium perfringens  epsilon toxin, ricin toxin,  pseudomonas  exotoxin, exotoxins, neurotoxins, cytokines, cytokine receptors, monokines, monokine receptors, plant pollens, animal dander, and dust mites. 
     
     
       7. The frozen immunogenic composition of  claim 1 , wherein the at least one antigen comprises at least one viral antigen or component derived from a virus. 
     
     
       8. The frozen immunogenic composition of  claim 7 , wherein the at least one viral antigen comprises at least one viral antigen or component derived from a coronavirus, a flavivirus, a human papilloma virus or an alphavirus. 
     
     
       9. The frozen immunogenic composition of  claim 1 , (g) wherein the frozen immunogenic composition is further processed by lyophilization to form an essentially dried immunogenic composition. 
     
     
       10. The frozen immunogenic composition of  claim 1 , wherein the aluminum-salt adjuvant is aluminum hydroxide. 
     
     
       11. The frozen immunogenic composition of  claim 1 , wherein the volatile salt is ammonium acetate or ammonium formate. 
     
     
       12. The frozen immunogenic composition of  claim 1 , wherein the glass-forming agent is selected from the group consisting of trehalose, sucrose, and hydroxyethyl starch. 
     
     
       13. The frozen immunogenic composition of  claim 9 , wherein the essentially dried immunogenic composition is reconstituted and adjuvant particles in the reconstituted immunogenic composition have reduced aggregation and agglomeration when compared to a composition without a volatile salt. 
     
     
       14. The frozen immunogenic composition of  claim 9 , wherein the essentially dried immunogenic composition is reconstituted in a pharmaceutically acceptable diluent. 
     
     
       15. The frozen immunogenic composition of  claim 1 , wherein the volatile salt is ammonium acetate or ammonium formate and the glass-forming agent is selected from the group consisting of trehalose, sucrose and hydroxyethyl starch. 
     
     
       16. A kit comprising the frozen immunogenic composition of  claim 1 , and at least one container.